Trifluoroacetic acid → 2,2-Difluoro-N-((1S,2R)-1-fluoromethyl-2-hydroxy-2-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-ethyl)-acetamide

HRID 525573Notes

Reaction equation

HRID 525573 reaction equation
[F:1][CH:2]([F:34])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[N:20][C:21]([CH:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[CH3:25])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[F:34][CH:2]([F:1])[C:3]([NH:5][C@H:9]([CH2:10][F:11])[C@H:8]([OH:7])[C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:19]=[N:20][C:21]([CH:24]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[CH3:25])=[CH:22][CH:23]=2)=[CH:16][CH:17]=1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866954552,2-Difluoro-1-((4S,5R)-4-fluoromethyl-2,2-dimethyl-5-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-oxazolidin-3-yl)-ethanone

Product 1

HCID 866954542,2-Difluoro-N-((1S,2R)-1-fluoromethyl-2-hydroxy-2-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-ethyl)-acetamideYield 56.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2,2-Difluoro-1-((4S,5R)-4-fluoromethyl -2,2-dimethyl-5-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-oxazolidin-3-yl)-ethanone (0.101 g, 0.309 mmol) in CH2Cl2 (5 mL) is added trifluoroacetic acid (1 mL) at 0° C. Reaction mixture is allowed to stir at room temperature for 4 hours. The solvent evaporated in vacuo and the crude material is diluted with saturated bicarbonate solution and extract with 10% MeOH:DCM. Combined organic layer dried over sodium sulphate, concentrated and purified by combiflash using 5% methanol:CH2Cl2 as eluent to afford desired compound (0.076 g): 1H NMR (400 MHz, CDCl3) δ: 1.33 (d, J=2.52 Hz, 3H), 2.32-2.35 (m, 2H), 2.49-2.50 (m, 2H), 3.55-3.57 (m, 4H), 3.59-3.60 (m, 1H), 4.29-4.30 (m, 1H), 4.32 (m, 0.5H), 4.40-4.44 (m, 0.5H), 4.54-4.55 (m, 0.5H), 4.64-4.66 (m, 0.5H), 4.88 (bs, 1H), 5.92 (d, J=3.96 Hz, 1H), 6.20 (t, J=53.72 Hz, 1H), 7.45 (d, J=8.24 Hz, 2H), 7.49 (d, J=8.24, 1H), 7.69 (d, J=8.28 Hz, 2H), 8.03-8.06 (dd, J1=8.2 Hz, J2=2.4 Hz, 1H), 8.80 (d, J=2.04 Hz, 1H), 8.86 (d, J=8.56 Hz, 1H). LC-Ms (m/z): 438.1[M+H].

Workup

  1. customReaction mixture
  2. customThe solvent evaporated in vacuo
  3. additionthe crude material is diluted with saturated bicarbonate solution
  4. extractionextract with 10% MeOH
  5. dry with materialCombined organic layer dried over sodium sulphate
  6. concentrationconcentrated
  7. custompurified by combiflash

Sources & evidence

ORD record
ord-344c0c29d48b44879b659b167721badc
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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